Functional roles of human kallikrein-related peptidases

Abstract

Kallikrein-related peptidases constitute a single family of 15 (chymo)trypsin-like proteases (KLK1-15) with pleiotropic physiological roles. Aberrant regulation of KLKs has been associated with diverse diseases such as hypertension, renal dysfunction, skin disorders, inflammation, neurodegeneration, and cancer. Recent studies suggested that coordinated activation and regulation of KLK activity are achieved via a complex network of interactions referred to as the "KLK activome." However, it remains to be validated whether these hypothetical KLK activation cascade pathways are operative in vivo. In addition, KLKs have emerged as versatile signaling molecules. In summary, KLKs represent attractive biomarkers for clinical applications and potential therapeutic targets for common human pathologies.

FIGURE 1.

Regulatory KLK cascades in normal physiology and disease states. Proteolytic activities produced by zymogen activation via the KLK activome are involved in processes of skin desquamation, innate immunity, hypertension, semen liquefaction, neurodegeneration, and tumor-promoting or -inhibiting effects. Notably, certain KLKs exert pleiotropic functions by activating molecules involved in multiple processes, e.g. cathelicidin, which is involved in skin desquamation and innate immunity. It should be noted that only those KLKs that have been shown to activate recombinant pro-KLKs were included in the depicted KLK activome. IGF1R, IGF 1 receptor; a-syn, α-synuclein; MBP, myelin basic protein; BK, bradykinin; B1, bradykinin-1.